Central to the success of the UK-ADC over the past 25 years is Clinical Core productivity that has allowed the development and perpetuation of a large longitudinally-followed, well-characterized, continuously-replenishing cohort focused on normal aging and early transitional disease states. All subjects undergo autopsy at death supporting clinical-pathologic research in aging and dementia. This practice has allowed major contributions in the area of clinical-pathological correlative studies and our understanding of early preclinical and predementia disease states such as mild cognitive impairment (MCI). UK-ADC productivity in terms of contributions to national collaborative initiatives such as NACC (2nd in overall productivity), ADCS (2nd in overall productivity), ADNI (2nd in overall productivity), NCRAD (597 normal control cell lines), and GWAS/ADGC is well recognized by involved researchers participating in these initiatives. The Clinical Core of the UK-ADC has contributed to the success of 31 independent research studies using living subjects (in addition to the many that rely on our data for work in the area of biospecimens and neuropathology), and has led to an impressive 159 publications supported by this core over the last funding cycle. In the upcoming cycle, under the leadership of Dr. Greg Jicha, we will focus our efforts on supporting investigations in the detection and treatment of preclinical AD and MCI of the AD-type as outlined in the new proposed NIA criteria released at ICAD 2010. As such, our center is in critical transition, developing and expanding biomarker capabilities (target normal to MCI/dementia transitions, n=270 over the next funding period, and n=50 high risk normals for the development of preclinical AD) while maintaining the size of our existing cohort to ensure sufficient transitions from normal to MCI and dementia (n=500 normals and n=300 impaired), continuing to work towards the development of more sensitive cognitive measures recommended by the NIA proposed criteria for preclinical AD, and fully supporting our continued leadership position in the area of clinical-pathological correlative studies under the NR Core leadership of Dr. Peter Nelson. The clinical core fully supports the leadership role of Dr. Linda Van Eldik as center director, after the loss of Dr. Markesbery earlier this year. We are committed to remaining one of the top ADCs in the nation and across the globe. We have further strengthened our resolve and commitment to advancing research and moving diagnostic strategies and therapeutic development forward as we transition into a new era of research with the NIA..